Senile Dementia, Alzheimer's Type (SDAT) is one of the most common yet most poorly understood of neurologic disorders. The classic triad of lesions encountered in the brains of SDAT cases and those of aged individuals are neurofibrillary tangles, senile plaques and granulovacuolar degeneration. Although the extent of involvement in the brain correlates clinically with the degree of dementia, we know nothing about the pathogenesis of these lesions. Recent studies have pointed to the possible role of excess aluminum in the pathogenesis of SDAT. Through the use of scanning electron microscopy with electron probe analysis, we have developed a method for the identification of tangle-bearing neurons in brain sections coupled with evaluation of the elemental content of those cells. Our preliminary data indicate that tangle-bearing neurons contain focal intranuclear concentrations of aluminum and silicon. Noninvolved neurons have failed to demonstrate similar accumulations. Through systematic study of randomly selected neurons in various portions of the brain, we propose to evaluate and characterize the apparent association of these focal intracellular concentrations of trace elements to the presence of the neurofibrillary tangle. We intend to evaluate the association of aluminum and silicon concentrations within neurons of SDAT cases, non-demented individuals of increasing age, patients with dialysis dementia, Down's syndrome and rabbits with experimental aluminum encephalopathy. Considering our lack of understanding of the pathogenesis of senility and aging changes in the brain, the association of these trace elements to the tangle-containing neuron needs careful documentation and clarification.